Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis via Negativ

Olfactomedin 4 通过 Negativ 抑制前列腺癌细胞的生长和转移

• 批准号: 10929107
• 负责人: GRIFFIN RODGERS
• 金额: $ 64.05万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10929107
• 关键词: 13q12; 13q14; 14q; Adult; American; Anterior; BRCA2 gene; Bioinformatics; Biological; Biological Process; C57BL/6 Mouse; CD44 gene; Cadherins; Cancer Cell Growth; Cancer Etiology; Cathepsins; Cell Adhesion; Cell Proliferation; Cell Separation; Cell physiology; Cell surface; Cells; Cessation of life; Chromosomes; Colon Carcinoma; Colonic Neoplasms; Development; Diagnosis; E-Cadherin; Ectopic Expression; Epithelial Cells; Epithelium; Evaluation; Exons; FOXO1A gene; Family; Family member; Gene Expression Regulation; Genes; Genitourinary system; Goals; Homeostasis; Human; Human Genome; In Vitro; Inflammation; Invaded; Lectin; Loss of Heterozygosity; Malignant neoplasm of prostate; Messenger RNA; Metadata; Metastatic Neoplasm to the Bone; Modeling; Molecular; Mus; Natural Immunity; Neoplasm Metastasis; OLFM4 gene; Organoids; Prognosis; Prostate; Prostatic Epithelium; Prostatic Neoplasms; Proteins; RB1 gene; Reporter; Reporting; Retinoblastoma; Seminal fluid; Serum; Signal Pathway; Solid Neoplasm; Stomach Neoplasms; Stromal Cell-Derived Factor 1; Susceptibility Gene; Tissues; Tube; Tumor Suppressor Genes; Tumor Suppressor Proteins; Up-Regulation; Urethra; Xenobiotic Metabolism; advanced prostate cancer; cancer type; cell preparation; forkhead protein; improved; in vivo; male; malignant breast neoplasm; malignant stomach neoplasm; men; migration; novel; olfactomedin; postnatal development; prostate cancer cell; prostate cancer progression; single-cell RNA sequencing

Olfactomedin4 (Olfm4) is expressed in normal mouse prostate. However, Olfm4+ cells in the murine prostate have not been well characterized. In this study, we generated an Olfm4eGFP reporter mouse line with C57BL/6 mice and investigated the distribution of Olfm4/eGFP-expressing cells during postnatal development from P1, P7, P14, P20, P42, P56 to adult male mouse prostate and urethral tube. We observed Olfm4/eGFP expression in urogenital and prostatic epithelial cells during early postnatal development, which persisted into adulthood in urethral-tube and anterior-prostate (AP) epithelium. We found Olfm4+ cells are E-cadherin+/CD44+/Foxa1+ and some of subpopulation are Ck8+/Ck5+/Sca-1-/Ck4-/Syn- in the adult mouse AP epithelium. Functional studies of single-cell preparations of Olfm4/eGFP-expressing cells isolated from adult Olfm4eGFP mouse prostate demonstrated that Olfm4+ cells can grow and form colonies, spheres, or organoids in culture. Bioinformatic analysis of Olfm4+ cells using single-cell RNA sequencing meta data in adult mouse urethra (GSE145865) identified upregulation of genes related to cell and tissue migration and development, as well as upregulation of xenobiotic metabolism signaling pathways. In conclusion, Olfm4eGFP mouse is a novel model to further study Olfm4's biological functions and Olfm4+ cells may contribute importantly to cellular processes supporting development and homeostasis of the epithelium in murine prostate and urethral tube.

Olfactomedin4 (Olfm4) 在正常小鼠前列腺中表达。然而，小鼠前列腺中的 Olfm4+ 细胞尚未得到很好的表征。在这项研究中，我们用 C57BL/6 小鼠构建了 Olfm4eGFP 报告小鼠系，并研究了 Olfm4/eGFP 表达细胞在出生后发育过程中的分布，从 P1、P7、P14、P20、P42、P56 到成年雄性小鼠前列腺和尿道管。我们在产后早期发育过程中观察到 Olfm4/eGFP 在泌尿生殖和前列腺上皮细胞中的表达，这种表达在尿道管和前前列腺（AP）上皮中持续到成年。我们发现成年小鼠 AP 上皮细胞中的 Olfm4+ 细胞为 E-cadherin+/CD44+/Foxa1+，部分亚群为 Ck8+/Ck5+/Sca-1-/Ck4-/Syn-。对从成年 Olfm4eGFP 小鼠前列腺分离的 Olfm4/eGFP 表达细胞的单细胞制剂的功能研究表明，Olfm4+ 细胞可以在培养物中生长并形成集落、球体或类器官。使用成年小鼠尿道 (GSE145865) 中的单细胞 RNA 测序元数据对 Olfm4+ 细胞进行生物信息分析，发现与细胞和组织迁移和发育相关的基因上调，以及外源代谢信号通路上调。总之，Olfm4eGFP 小鼠是进一步研究 Olfm4 生物学功能的新模型，Olfm4+ 细胞可能对支持小鼠前列腺和尿道管上皮发育和稳态的细胞过程做出重要贡献。

项目成果

Characterization of olfactomedin 4+ cells in prostate and urethral-tube epithelium during murine postnatal development and in adult mice.

• DOI: 10.1038/s41598-023-37320-9
• 发表时间: 2023-06-25
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Li, Hongzhen;Chaitankar, Vijender;Cui, Lena;Chen, Weiping;Chin, Kyung;Zhu, Jianqiong;Liu, Wenli;Rodgers, Griffin P.
• 通讯作者: Rodgers, Griffin P.

Olfactomedin 4 deficiency promotes prostate neoplastic progression and is associated with upregulation of the hedgehog-signaling pathway.

• DOI: 10.1038/srep16974
• 发表时间: 2015-11-19
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Li H;Liu W;Chen W;Zhu J;Deng CX;Rodgers GP
• 通讯作者: Rodgers GP

Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC.

• DOI: 10.1038/s41598-020-78774-5
• 发表时间: 2020-12-14
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Li H;Chaitankar V;Zhu J;Chin K;Liu W;Pirooznia M;Rodgers GP
• 通讯作者: Rodgers GP